A major thrust of contemporary applied research is the search for improved in vivo imaging methodologies that can replace the present use of biopsy, a painful and invasive procedure for histological examination of tissue. Unfortunately none of the currently available non-invasive imaging technologies have the resolution that can be obtained with histological examination of tissue. Using phase-sensitive low coherence interferometry the objective of the proposed research is the development of a fiber-based differential phase contrast optical coherence tomography (DPC-OCT) system capable of a high-resolution quantitative phase contrast imaging of biological tissue that are comparable to histology. The proposed high resolution DPC-OCT system will be capable of imaging individual cells with sub-cellular resolution without use of exogenous stains or contrast agents by measurement of the phase contrast between cellular components. DPC-OCT combines the phase contrast imaging capability of a phase contrast microscope and high sensitivity and high depth resolution of OCT to obtain quantitative phase contrast microscopic images. Addition of phase contrast measuring capability to an OCT system makes possible imaging of specimen with very small spatial refractive index variations. Since tissue constituents are primarily distinguished optically by spatial variation in refractive index, DPC-OCT has the potential to dramatically improve the resolution of conventional OCT images. Although we have obtained DPC-OCT images of single layered cells with sub-cellular resolution, quantitative phase contrast imaging of a complex and multilayered structure such as tissue is challenging. Specific aims of the proposal are, . Construct and develop a high-resolution fiber DPC-OCT system for rapid quantitative phase contrast imaging of biological tissue. . Develop a robust image reconstruction procedure to obtain depth resolved 3-D quantitative phase contrast images from recorded interference fringe intensity signals; and . Test and verify the operation of the constructed fiber DPC-OCT system with 1) tissue phantoms, and 2) ex vivo human tissue samples. Successful completion of project aims will result in the development of a non-invasive imaging modality with unprecedented resolution that will be a very valuable tool in a variety of clinical diagnostic and monitoring applications.